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Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs

Lookup NU author(s): Dr Morvern Morrison, Dr Anders Andreasson, Catriona Charlton, Dr Alisha Chhatwal, Dr Bill ScottORCiD, Dr Lee Borthwick, Professor Andrew FisherORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2021 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.Background: Transplantation is an effective treatment for end-stage lung disease, but the donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of extended criteria organs enables functional assessment to facilitate clinical decision-making around utilization, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remain to be determined. Methods: We used RNA sequencing of lung tissue to delineate changes in gene expression occurring in 10 donor lungs undergoing EVLP and compare lungs that were deemed non-transplantable (n = 4) to those deemed transplantable (n = 6) following perfusion. Results: We found that lungs deemed unsuitable for transplantation had increased induction of innate immune pathways and lower expression of oxidative phosphorylation related genes. Furthermore, the expression of SCGB1A1, a gene encoding an anti-inflammatory secretoglobin CC10, and other club cell genes was significantly decreased in non-transplantable lungs, while CHIT-1 was increased. Using a larger validation cohort (n = 17), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable from non-transplantable lungs (AUC.81). Conclusions: Together, our data identify novel biomarkers that may assist with pre-transplant lung assessment, as well as pathways that may be amenable to therapeutic intervention during EVLPAQ6.

Publication metadata

Author(s): Ferdinand JR, Morrison MI, Andreasson A, Charlton C, Chhatwal AK, Scott WE, Borthwick LA, Clatworthy MR, Fisher AJ

Publication type: Article

Publication status: Published

Journal: Clinical Transplantation

Year: 2022

Volume: 36

Issue: 4

Print publication date: 01/04/2022

Online publication date: 26/12/2021

Acceptance date: 20/12/2021

Date deposited: 29/06/2023

ISSN (print): 0902-0063

ISSN (electronic): 1399-0012

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1111/ctr.14570

DOI: 10.1111/ctr.14570

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